Method and device for electrogram based estimation of qrs duration

ABSTRACT

Methods and devices are provided that collect intra-cardiac electrogram (EGM) signals over first and second sensing channels (channel-1 and channel-2 EGM signals, respectively) associated with an event of interest that includes a right ventricle (RV) and a left ventricle (LV), determine first, second and third global characteristics (GC) from the channel-1 and channel-2 EGM signals, and define a QRS start time within at least one of the EGM signals; and determine a threshold crossing. The methods and systems compare at least one of the first, second and third GC to the threshold crossing, select one of the first, second and third GC based on the comparing; defining a QRS end time, within at least one of the channel-1 and channel-2 EGM signals based on the one of the first, second and third GC selected, and calculate a QRS duration based on the QRS start time and QRS end time.

REFERENCE TO RELATED APPLICATIONS

The present application is a continuation-in-part application of, andclaims priority to, U.S. application Ser. No. 15/851,342, Titled “METHODAND DEVICE FOR ELECTROGRAM BASED ESTIMATION OF QRS DURATION” which wasfiled on Dec. 21, 2017, the complete subject matter of which isexpressly incorporated herein by reference in its entirety.

BACKGROUND

Embodiments of the present disclosure generally relate to methods anddevices for estimating a duration of a QRS complex based on intracardiacelectrograms signals.

Implantable medical device programmable cardiac resynchronizationtherapy (CRT) based on various parameters. Changes in the CRT parametershave been shown to have an impact on clinical outcomes. Nonlimitingexamples of CRT parameters include atrioventricular and interventricularactivation delays (AVD and VVD, respectively), electrode configuration,and selection of paced ventricular chambers. Identifying a desired setof CRT parameters relies on an accurate assessment of relative cardiacfunction. Echocardiography and invasive left ventricular (LV) pressuremeasurements have been considered the gold standard for direct,comprehensive hemodynamic optimization of CRT parameters. However,echocardiography and LV pressure measurements are costly, timeconsuming, and must occur in a clinical environment.

Separately, surface electrocardiogram (ECG) signals have been utilizedas a simpler alternative for assessing relative cardiac function. ECGsignals may be utilized to determine whether electrical synchrony hasbeen restored by CRT. More specifically, an ECG signal may be analyzedfor a broad or narrow QRS complex. Dyssynchrony is typically associatedwith a broad QRS complex, while synchrony is typically associated with anarrow QRS complex.

However, the cardiovascular status of an individual patient constantlychanges. Accordingly, continuous evaluation of, and adaptation to, thecurrent cardiovascular status is necessary in order to maintain anoptimal CRT parameter set. The use of surface ECG electrodes to collectECG signals represents a cumbersome, time-consuming and difficult systemto provide continuous, ambulatory monitoring of the cardiac response toCRT.

SUMMARY

In accordance with an embodiment, a method is provided, comprisingcollecting an intra-cardiac electrogram (EGM) signal associated with anevent of interest and determining an global amplitude characteristic(GAC) and a global slope characteristic (GSC) from the EGM signal undercontrol of one or more processors within an implantable medical device(IMD). The method comprises defining a QRS start time, within the EGMsignal, based on the GSC and determining a local amplitudecharacteristic (LAC) for a segment of the EGM signal within a searchwindow of the GAC under control of one or more processors within animplantable medical device (IMD). The method further comprises defininga QRS end time, within the EGM signal, based on the LAC, and calculatinga QRS duration based on the QRS start time and QRS end time undercontrol of one or more processors within an implantable medical device(IMD).

Optionally, the GAC may represent a global amplitude minimum experiencedby the EGM signal over the event of interest. The GSC may represent aglobal slope minimum experienced by the EGM signal over the event ofinterest. The defining the QRS start time further may comprise definingthe QRS start time as a last time point along the QRS complex before apoint in time at which the GSC exhibited at least one of: a derivativeof the EGM signal exceeds the global slope characteristic by apredetermined slope factor or the EGM signal exceeds the globalamplitude minimum by a predetermined amplitude factor.

Optionally the determining the GSC may include calculating derivativesat points along the EGM signal over a search window that precedes theGAC and determining the global slope minimum in a negative directionbased on the derivatives. The method may further comprise reducing theQRS start time by an amount corresponding to an isoelectric drop.

Optionally, the determining the LAC may comprise determining a localamplitude maximum that occurs within a search window after the GAC; andidentifying threshold crossings of the EGM signal that surround thelocal amplitude maximum, the threshold crossings representing points atwhich the EGM signal cross a threshold amplitude that is defined basedon the local amplitude maximum. The QRS end time may be determined tocorrespond to a point in time along the EGM signal at a set pointbetween the threshold crossings.

Optionally, the method may, further comprise determining whether adeflection spike occurs prior to the QRS start time, verifying whetherthe deflection spike represents a local maximum amplitude, and adjustingthe QRS start time based on the verifying to a point in time before thedeflection spike. The method may also comprising determining whether adeflection spike occurs prior to the QRS start time, verifying whether aslope of the EGM signal within a search window prior to the deflectionspike falls below the global slope characteristic by a slope factor, andadjusting the QRS start time based on the verifying to a point in timebefore the deflection spike.

In accordance with an embodiment, a system is provided comprising animplantable lead having electrodes configured to be located proximate toa heart, the electrodes defining a sensing vector through a region ofinterest in the heart. The system includes memory to store programinstructions; and a processor. The processor, when executing the programinstructions, is configured to collect an intra-cardiac electrogram(EGM) signal along the sensing vector, the EGM signal associated with anevent of interest; determine an global amplitude characteristic (GAC)and a global slope characteristic (GSC) from the EGM signal. Theprocessor is further configured to define a QRS start time, within theEGM signal, based on the GSC; determine a local amplitude characteristic(LAC) for a segment of the EGM signal within a search window of the GAC,define a QRS end time, within the EGM signal, based on the LAC, andcalculate a QRS duration based on the QRS start and QRS end.

Optionally, the GAC may represent a global amplitude minimum experiencedby the EGM signal over the event of interest. The GSC may represent aglobal slope minimum experienced by the EGM signal over the event ofinterest.

Optionally, the processor may be configured to define the QRS start timeas a last time point along the QRS complex before a point in time atwhich the GSC exhibited at least one of: I) a slope of the EGM signalexceeds the global slope minimum by a predetermined slope factor or II)the EGM signal exceeds the global amplitude minimum by a predeterminedamplitude factor. The processor may also be configured to calculatederivatives at points along the EGM signal over a search window thatprecedes the GAC and to determine the global slope minimum in a negativedirection based on the derivatives.

Optionally, the system may further comprise reducing the QRS start timeby an amount corresponding to an isoelectric drop. The determining theLAC may comprise determining a local amplitude maximum that occurswithin a time window after the GAC; and identifying threshold crossingsof the EGM signal that surround the local amplitude maximum, thethreshold crossings representing points at which the EGM signal cross athreshold amplitude that is defined based on the local amplitudemaximum. The QRS end time may be determined to correspond to a point intime along the EGM signal at a set point between the thresholdcrossings.

Optionally, the processor may further be configured to determine whethera deflection spike occurs prior to the QRS start time, verifying whetherthe deflection spike represents a local maximum amplitude, and adjustingthe QRS start time based on the verifying to a point in time before thedeflection spike. The processor may further be configured to determinewhether a deflection spike occurs prior to the QRS start time, verifyingwhether a slope of the EGM signal within a time window prior to thedeflection spike falls below the global slope characteristic by a slopefactor, and, based on the verifying, adjusting the QRS start time to apoint in time before the deflection spike.

In accordance with embodiments herein, a method is provided thatcomprises under control of one or more processors within an implantablemedical device (IMD); collecting intra-cardiac electrogram (EGM) signalsover first and second sensing channels (channel-1 and channel-2 EGMsignals, respectively) associated with an event of interest thatincludes a right ventricle (RV) and a left ventricle (LV); determiningfirst, second and third global characteristics (GC) from the channel-1and channel-2 EGM signals; defining a QRS start time within at least oneof the EGM signals; determine a threshold crossing; comparing at leastone of the first, second and third GC to the threshold crossing;selecting one of the first, second and third GC based on the comparing;defining a QRS end time, within at least one of the channel-1 andchannel-2 EGM signals, based on the comparing and based on the one ofthe first, second and third GC selected; and calculating a QRS durationbased on the QRS start time and QRS end time.

Additionally or alternatively, the threshold crossing represents atleast one of a positive-negative crossing or the third GC, the third GCrepresenting a global amplitude minimum experienced by the channel-2 EGMsignal over the event of interest. Optionally, the first GC and secondGC represent first and second global amplitude characteristics (GAC) ofthe channel-1 EGM signal, and the third GC represents a first GAC of thechannel-2 EGM signal. Optionally, the first GAC represents an RV peak,the second GAC represents an RV valley and the third GAC represents anLV valley. Optionally, the method further comprises identifying a pacingmode implemented when collecting the channel-1 and channel-2 EGMsignals, the comparing including comparing the at least one of thefirst, second and third GC to different first and second thresholdcrossings based on the pacing mode. Optionally, when the pacing mode isone of a left ventricular multi-site pacing or multi-point pacing, thethreshold crossing corresponding to the first GC having a value that isboth positive and greater than or equal to a select percentage of thesecond GC. Optionally, when the pacing mode is one of biventricularpacing or left ventricular single site pacing, the threshold crossingcorresponding to the first GC having a value that is positive.Optionally, when the pacing mode is one of a left ventricular multi-sitepacing or multi-point pacing, the defining including defining the QRSend as either i) a time when the channel-1 EGM signal reaches a setrelation to an RV peak corresponding to the first GC or ii) a time whenthe channel-1 EGM signal reaches a set recovery relation to an RV valleycorresponding to the second GC. Optionally, when the pacing mode is oneof biventricular pacing or left ventricular single site pacing, thedefining including defining the QRS end as either i) a time when thechannel-1 EGM signal reaches an RV peak corresponding to the first GC orii) a time when the channel-1 EGM signal reaches an RV valleycorresponding to the second GC. Optionally, the first and third GCcorresponding to an RV peak in the channel-1 EGM signal and an LV valleyin the channel-2 EGM signal, respectively, the method further comprisingidentifying that the channel-1 and channel-2 EGM signals were collectedduring intrinsic ventricular activity, and based thereon defining theQRS end as a later time of the RV peak and the LV valley.

In accordance with embodiments herein, a system is provided thatcomprises electrodes configured to be located proximate to a heart, theelectrodes defining channel-1 and channel-2 sensing channels through aregion of interest in the heart that includes a right ventricle (RV) anda left ventricle (LV); memory to store program instructions; and aprocessor that, when executing the program instructions, is configuredto: collect intra-cardiac electrogram (EGM) signals over first andsecond sensing channels (channel-1 and channel-2 EGM signals,respectively) associated with an event of interest; determine first,second and third global characteristics (GC) from the channel-1 andchannel-2 EGM signals; define a QRS start time within at least one ofthe EGM signals; determine a threshold crossing; compare at least one ofthe first, second and third GC to the threshold crossing; select one ofthe first, second and third GC based on the comparing; define a QRS endtime, within at least one of the channel-1 and channel-2 EGM signals,based on the comparing and based on the one of the first, second andthird GC selected; and calculate a QRS duration based on the QRS starttime and QRS end time.

Optionally, the processor is configured to identify the thresholdcrossing as at least one of a positive-negative crossing or the thirdGC, the third GC representing a global amplitude minimum experienced bythe channel-2 EGM signal over the event of interest. Optionally, theprocessor is configured to define the first GC and second GC as firstand second global amplitude characteristics (GAC) of the channel-1 EGMsignal, and define the third GC as a first GAC of the channel-2 EGMsignal. Optionally, the first GAC represents an RV peak, the second GACrepresents an RV valley and the third GAC represents an LV valley.Optionally, the processor is configured to identify a pacing modeimplemented when collecting the channel-1 and channel-2 EGM signals, thecompare the at least one of the first, second and third GC to differentfirst and second threshold crossings based on the pacing mode.Optionally, when the pacing mode is one of a left ventricular multi-sitepacing or multi-point pacing, the processor is configured to designatethe threshold crossing to correspond to the first GC having a value thatis both positive and greater than or equal to a select percentage of thesecond GC. Optionally, when the pacing mode is one of biventricularpacing or left ventricular single site pacing, the processor isconfigured to designate the threshold crossing to correspond to thefirst GC having a value that is positive. Optionally, when the pacingmode is one of a left ventricular multi-site pacing or multi-pointpacing, the processor is configured to define the QRS end as either i) atime when the channel-1 EGM signal reaches a set relation to an RV peakcorresponding to the first GC or ii) a time when the channel-1 EGMsignal reaches a set recovery relation to an RV valley corresponding tothe second GC. Optionally, when the pacing mode is one of biventricularpacing or left ventricular single site pacing, the processor isconfigured to define the QRS end as either i) a time when the channel-1EGM signal reaches an RV peak corresponding to the first GC or ii) atime when the channel-1 EGM signal reaches an RV valley corresponding tothe second GC. Optionally, the processor is configured to designate thefirst and third GC to correspond to an RV peak in the channel-1 EGMsignal and an LV valley in the channel-2 EGM signal, respectively, theprocessor is configured to identify that the channel-1 and channel-2 EGMsignals were collected during intrinsic ventricular activity, and basedthereon define the QRS end as a later time of the RV peak and the LVvalley.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an implantable medical device and external devicecoupled to a heart in a patient and implemented in accordance with oneembodiment.

FIG. 2 shows an exemplary IMD 100 that is implanted into the patient aspart of the implantable cardiac system in accordance with embodimentsherein.

FIGS. 3A and 3B illustrate a process for estimating a duration of a QRScomplex from intracardiac electrograms in accordance with embodimentsherein.

FIG. 3C illustrates a process for determining synchrony or dyssynchronywithin physiologic behavior of the heart in accordance with embodimentsherein.

FIG. 4A illustrates an example EGM signal for one cardiac cycle alongwith notations for characteristics of interest analyzed in accordancewith embodiments herein.

FIG. 4B illustrates an example EGM signal for one cardiac cycle alongwith notations for characteristics of interest analyzed in accordancewith embodiments herein.

FIG. 5 illustrates a functional block diagram of the external devicethat is operated in accordance with the processes described herein andto interface with implantable medical devices as described herein.

FIG. 6A illustrates a process for estimating a duration of a QRS complexfrom intracardiac electrograms in accordance with alternativeembodiments herein.

FIG. 6B illustrates a method for defining a QRS end time in accordancewith embodiments herein.

FIG. 7 illustrates examples of EGM signals collected over first andsecond sensing channels in connection with different intrinsic or pacingmodes.

DETAILED DESCRIPTION

It will be readily understood that the components of the embodiments asgenerally described and illustrated in the figures herein, may bearranged and designed in a wide variety of different configurations inaddition to the described example embodiments. Thus, the following moredetailed description of the example embodiments, as represented in thefigures, is not intended to limit the scope of the embodiments, asclaimed, but is merely representative of example embodiments.

Reference throughout this specification to “one embodiment” or “anembodiment” (or the like) means that a particular feature, structure, orcharacteristic described in connection with the embodiment is includedin at least one embodiment. Thus, appearances of the phrases “in oneembodiment” or “in an embodiment” or the like in various placesthroughout this specification are not necessarily all referring to thesame embodiment.

Furthermore, the described features, structures, or characteristics maybe combined in any suitable manner in one or more embodiments. In thefollowing description, numerous specific details are provided to give athorough understanding of embodiments. One skilled in the relevant artwill recognize, however, that the various embodiments can be practicedwithout one or more of the specific details, or with other methods,components, materials, etc. In other instances, well-known structures,materials, or operations are not shown or described in detail to avoidobfuscation. The following description is intended only by way ofexample, and simply illustrates certain example embodiments.

The methods described herein may employ structures or aspects of variousembodiments (e.g., systems and/or methods) discussed herein. In variousembodiments, certain operations may be omitted or added, certainoperations may be combined, certain operations may be performedsimultaneously, certain operations may be performed concurrently,certain operations may be split into multiple operations, certainoperations may be performed in a different order, or certain operationsor series of operations may be re-performed in an iterative fashion. Itshould be noted that, other methods may be used, in accordance with anembodiment herein. Further, wherein indicated, the methods may be fullyor partially implemented by one or more processors of one or moredevices or systems. While the operations of some methods may bedescribed as performed by the processor(s) of one device, additionally,some or all of such operations may be performed by the processor(s) ofanother device described herein.

Embodiments may be implemented in connection with one or moreimplantable medical devices (IMDs). Non-limiting examples of IMDsinclude one or more of neurostimulator devices, implantable leadlessmonitoring and/or therapy devices, and/or alternative implantablemedical devices. For example, the IMD may represent a cardiac monitoringdevice, pacemaker, cardioverter, cardiac rhythm management device,defibrillator, neurostimulator, leadless monitoring device, leadlesspacemaker and the like. For example, the IMD may include one or morestructural and/or functional aspects of the device(s) described in U.S.Pat. No. 9,333,351 “Neurostimulation Method And System To Treat Apnea”and U.S. Pat. No. 9,044,610 “System And Methods For Providing ADistributed Virtual Stimulation Cathode For Use With An ImplantableNeurostimulation System”, which are hereby incorporated by reference.Additionally or alternatively, the IMD may include one or morestructural and/or functional aspects of the device(s) described in U.S.Pat. No. 9,216,285 “Leadless Implantable Medical Device Having RemovableAnd Fixed Components” and U.S. Pat. No. 8,831,747 “LeadlessNeurostimulation Device And Method Including The Same”, which are herebyincorporated by reference. Additionally or alternatively, the IMD mayinclude one or more structural and/or functional aspects of thedevice(s) described in U.S. Pat. No. 8,391,980 “Method And System ForIdentifying A Potential Lead Failure In An Implantable Medical Device”and U.S. Pat. No. 9,232,485 “System And Method For SelectivelyCommunicating With An Implantable Medical Device”, which are herebyincorporated by reference.

The terms “minimum”, “maximum”, “optimal” and similar terminology, asused herein, do not necessarily refer to a particular point or numericvalue, but instead may refer to a range having a variation that would beexpected to have limited impact on a physiologic result. By way ofexample, an amplitude, slope or other characteristic of an EGM signalmay vary within a range (e.g., +/−5%), while still being considered aminimum, maximum, or optimal value.

The terms “minimum” and “maximum” are without regard for positive ornegative values, and more generally may be used to refer to absolutevalues of an EGM signal. For example, a minimum may be a minimum“negative” or a minimum “positive” value. Similarly, a maximum may be amaximum “negative” or a maximum “positive” value.

The term “global” is used throughout to refer to a characteristic of anEGM signal for a complete cardiac cycle or heartbeat. For example, aglobal amplitude maximum, would represent a maximum amplitude exhibitedover the EGM signal for a complete cardiac cycle. As another example, aglobal slope maximum, would represent a maximum slope exhibited over theEGM signal for a complete cardiac cycle.

The term “local” is used throughout to refer to a characteristic of asegment of an EGM signal for a subsection or phase of a cardiac cycle orheartbeat. For example, a local amplitude maximum, would represent amaximum amplitude exhibited over a segment within the EGM signal for apart of a cardiac cycle (e.g., within a search window having a durationof a few milliseconds). As another example a local slope maximum, wouldrepresent a maximum slope exhibited over a segment within the EGM signalfor a part of a cardiac cycle. The EGM signal for one cardiac cycle maybe divided into multiple segments, each of which exhibits a localamplitude maximum and a local slope maximum within the differentcorresponding search windows.

Embodiments herein provide a closed-loop, implantable device-basedalternative to surface ECG based systems, where the implantabledevice-based solution is not limited to in-clinic measurements (e.g.,surface ECG). Embodiments herein provide implantable device-basedmethods and devices to estimate QRS duration solely based onintracardiac electrograms (EGMs). The QRS duration estimation may beimplemented as part of an IMD and medical platforms, such as anautomated synchronous atrial and ventricular CRT programming andoptimization workflow.

FIG. 1 illustrates an IMD 100 and external device 104 coupled to a heartin a patient and implemented in accordance with one embodiment. Theexternal device 104 may be a programmer, an external defibrillator, aworkstation, a portable computer, a personal digital assistant, a cellphone, a bedside monitor and the like. The IMD 100 may represent acardiac monitoring device, pacemaker, cardioverter, cardiac rhythmmanagement device, defibrillator, neurostimulator, leadless monitoringdevice, leadless pacemaker and the like, implemented in accordance withone embodiment of the present invention. The IMD 100 may be adual-chamber stimulation device capable of treating both fast and slowarrhythmias with stimulation therapy, including cardioversion,defibrillation, anti-tachycardia pacing and pacing stimulation, as wellas capable of detecting heart failure, evaluating its severity, trackingthe progression thereof, and controlling the delivery of therapy andwarnings in response thereto. The IMD 100 may be controlled to senseatrial and ventricular waveforms of interest, discriminate between twoor more ventricular waveforms of interest, deliver stimulus pulses orshocks, and inhibit application of a stimulation pulse to a heart basedon the discrimination between the waveforms of interest and the like.Exemplary structures for the IMD 100 are discussed and illustrated inthe drawings herewith.

The IMD 100 includes a housing 101 that is joined to a header assembly109 that holds receptacle connectors connected to a right ventricularlead 110, a right atrial lead 112, and a coronary sinus lead 114,respectively. The leads 112, 114 and 110 measure cardiac signals of theheart. The right atrial lead 112 includes an atrial tip electrode 118and an atrial ring electrode 120. The coronary sinus lead 114 includes aleft atrial ring electrode 128, a left atrial coil electrode 130 and oneor more left ventricular electrodes 132-138 (e.g., also referred to asP1, M1, M2 and D1) to form a multi-pole LV electrode combination. Theright ventricular lead 110 includes an RV tip electrode 126, an RV ringelectrode 124, an RV coil electrode 122, and an SVC coil electrode 116.The leads 112, 114 and 110 detect EGM signals that are processed andanalyzed as described herein. The leads 112, 114 and 110 also deliverytherapies as described herein.

During implantation, the external device 104 is connected to one or moreof the leads 112, 114 and 110 through temporary inputs 103. The inputs103 of the external device 104 receive EGM signals from the leads 112,114 and 110 during implantation and display the EGM signals to thephysician on a display. Optionally, the external device 104 may not bedirectly connected to the leads 112, 114 and 110. Instead, the EGMcardiac signals sensed by the leads 112, 114 and 110 may be collected bythe IMD 100 and then transmitted wirelessly to the external device 104.Hence, the external device 104 receives the EGM cardiac signals throughtelemetry circuit inputs. The physician or another user controlsoperation of the external device 104 through a user interface.

Implantable Medical Device

FIG. 2 shows an exemplary IMD 100 that is implanted into the patient aspart of the implantable cardiac system. The IMD 100 may be implementedas a full-function biventricular pacemaker, equipped with both atrialand ventricular sensing and pacing circuitry for four chamber sensingand stimulation therapy (including both pacing and shock treatment).Optionally, the IMD 100 may provide full-function cardiacresynchronization therapy. For example, the IMD 100 may provide one ormore different pacing modes, such as left ventricular multisite (LVMS)pacing, multipoint pacing (MPP), biventricular (BiV) pacing or leftventricular single site (LVSS) pacing. Alternatively, the IMD 100 may beimplemented with a reduced set of functions and components. Forinstance, the IMD may be implemented without ventricular sensing andpacing.

The IMD 100 has a housing 101 to hold the electronic/computingcomponents. The housing 101 (which is often referred to as the “can”,“case”, “encasing”, or “case electrode”) may be programmably selected toact as the return electrode for certain stimulus modes. The housing 101further includes a connector (not shown) with a plurality of terminals102, 105, 106, 108, and 111. The terminals may be connected toelectrodes that are located in various locations within and about theheart. For example, the terminals may include: a terminal 102 to becoupled to an first electrode (e.g., a tip electrode) located in a firstchamber; a terminal 105 to be coupled to a second electrode (e.g., tipelectrode) located in a second chamber; a terminal 106 to be coupled toan electrode (e.g., ring) located in the first chamber; a terminal 108to be coupled to an electrode located (e.g., ring electrode) in thesecond chamber; and a terminal 111 to be coupled to an electrode (e.g.,coil) located in the SVC. The type and location of each electrode mayvary. For example, the electrodes may include various combinations ofring, tip, coil and shocking electrodes and the like.

The IMD 100 includes a programmable microcontroller 164 that controlsvarious operations of the IMD 100, including cardiac monitoring andstimulation therapy. The microcontroller 164 includes a microprocessor(or equivalent control circuitry), RAM and/or ROM memory, logic andtiming circuitry, condition machine circuitry, and I/O circuitry.

IMD 100 further includes a first chamber pulse generator 174 thatgenerates stimulation pulses for delivery by one or more electrodescoupled thereto. The pulse generator 174 is controlled by themicrocontroller 164 via control signal 176. The pulse generator 174 iscoupled to the select electrode(s) via an electrode configuration switch192, which includes multiple switches for connecting the desiredelectrodes to the appropriate I/O circuits, thereby facilitatingelectrode programmability. The switch 192 is controlled by a controlsignal 186 from the microcontroller 164.

In the example of FIG. 1, a single pulse generator 174 is illustrated.Optionally, the IMD 100 may include multiple pulse generators, similarto pulse generator 174, where each pulse generator is coupled to one ormore electrodes and controlled by the microcontroller 164 to deliverselect stimulus pulse(s) to the corresponding one or more electrodes.

Microcontroller 164 is illustrated to include timing control circuitry166 to control the timing of the stimulation pulses for CRT (e.g.,pacing rate, atrio-ventricular (AV) delay, atrial interconduction (A-A)delay, or ventricular interconduction (V-V) delay, etc.). The timingcontrol circuitry 166 may also be used for the timing of search windows,refractory periods, blanking intervals, noise detection windows, evokedresponse windows, alert intervals, marker channel timing, and so on.Microcontroller 164 also has an arrhythmia detector 168 for detectingarrhythmia conditions and a morphology detector 170 to review andanalyze one or more features of the morphology of cardiac signals.Although not shown, the microcontroller 164 may further include otherdedicated circuitry and/or firmware/software components that assist inmonitoring various conditions of the patient's heart and managing pacingtherapies.

The IMD 100 is further equipped with a communication modem(modulator/demodulator) 172 to enable wireless communication with otherdevices, implanted devices and/or external devices. In oneimplementation, the communication modem 172 may use high frequencymodulation of a signal transmitted between a pair of electrodes. As oneexample, the signals may be transmitted in a high frequency range ofapproximately 10-80 kHz, as such signals travel through the body tissueand fluids without stimulating the heart or being felt by the patient.

The communication modem 172 may be implemented in hardware as part ofthe microcontroller 164, or as software/firmware instructions programmedinto and executed by the microcontroller 164. Alternatively, thecommunication modem 172 may reside separately from the microcontrolleras a standalone component.

The IMD 100 includes sensing circuitry 180 selectively coupled to one ormore electrodes that perform sensing operations, through the switch 192to detect the presence of EGS signals along various sensing vectors. Thesensing circuitry 180 may include dedicated sense amplifiers,multiplexed amplifiers, or shared amplifiers. It may further employ oneor more low power, precision amplifiers with programmable gain and/orautomatic gain control, bandpass filtering, and threshold detectioncircuit to selectively sense the cardiac signal of interest. Theautomatic gain control enables the unit to sense low amplitude signalcharacteristics (e.g., atrial fibrillation). Switch 192 determines thesensing polarity of the cardiac signal by selectively closing theappropriate switches. In this way, the clinician may program the sensingpolarity independent of the stimulation polarity.

The output of the sensing circuitry 180 is connected to themicrocontroller 164 which, in turn, triggers or inhibits the pulsegenerator 174 in response to the absence or presence of certain types ofcardiac activity. The sensing circuitry 180 receives a control signal178 from the microcontroller 164 for purposes of controlling the gain,threshold, polarization charge removal circuitry (not shown), and thetiming of any blocking circuitry (not shown) coupled to the inputs ofthe sensing circuitry.

In the example of FIG. 1, a single sensing circuit 180 is illustrated.Optionally, the IMD 100 may include multiple sensing circuit, similar tosensing circuit 180, where each sensing circuit is coupled to one ormore electrodes and controlled by the microcontroller 164 to senseelectrical activity as EGM signals detected at the corresponding one ormore electrodes. The sensing circuit 180 may operate in a unipolarsensing configuration or in a bipolar sensing configuration. The IMD 100further includes an analog-to-digital (ND) data acquisition system (DAS)190 coupled to one or more electrodes via the switch 192 to samplecardiac signals across any pair of desired electrodes. The dataacquisition system 190 is configured to acquire intracardiac electrogramsignals, convert the raw analog data into digital data, and store thedigital data for later processing and/or telemetric transmission to anexternal device 104 (e.g., a programmer, local transceiver, or adiagnostic system analyzer). The data acquisition system 190 iscontrolled by a control signal 188 from the microcontroller 164.

In connection with FIG. 3A, an EGM signal is sensed along a far fieldsensing vector or channel that may be defined between variouscombinations of electrodes located within or proximate to the heart. Forexample, the sensing vector/channel may be between an RV coil electrodeand a can/housing of an IMD. Additionally or alternatively, the sensingvector/channel may be defined between electrode combinations that arespaced with a desired portion, or a majority of, the heart between theelectrodes. For example, the sensing vector may be between the RV coiland an LV electrode. Optionally, the sensing vector may be betweenanother RV electrode (e.g., tip or ring) and a can/housing of the IMDand/or an LV electrode. The electrodes may be configured to have aparticular anode/cathode combination. For example, the RV coil electrodemay be defined as the anode, while the can/housing of the IMD is definedas the cathode. The terms vector and channel are used interchangeablythroughout when discussing sensing vectors or sensing channels. In someexamples, first and second sensing channels/vectors may utilize firstand second combinations of electrodes, respectively. In otherembodiments, the first and second sensing channel select vectors mayutilize the same combination of electrodes to collect both first andsecond EGM signals, but utilizing different first and second sets ofsensing parameters (e.g. different pass bands, different sensitivitythresholds and the like).

The microcontroller 164 is coupled to a memory 152 by a suitabledata/address bus 162. The programmable operating parameters used by themicrocontroller 164 are stored in memory 152 and used to customize theoperation of the IMD 100 to suit the needs of a particular patient. Suchoperating parameters define, for example, CRT parameters, pacing pulseamplitude, pulse duration, electrode polarity, rate, sensitivity,automatic features, arrhythmia detection criteria.

The operating parameters of the IMD 100 may be non-invasively programmedinto the memory 152 through a telemetry circuit 154 in telemetriccommunication via communication link 150 with the external device 104(e.g., Bluetooth, low energy Bluetooth, or other wireless protocol). Thetelemetry circuit 154 allows intracardiac electrograms and statusinformation relating to the operation of the IMD 100 (as contained inthe microcontroller 164 or memory 152) to be sent to the external device104 through the established communication link 150.

The IMD 100 can optionally include magnet detection circuitry (notshown), coupled to the microcontroller 164, to detect when a magnet isplaced over the unit. A magnet may be used by a clinician to performvarious test functions of the unit 100 and/or to signal themicrocontroller 164 that the external programmer is in place to receiveor transmit data to the microcontroller 164 through the telemetrycircuits 154.

The IMD 100 can further include one or more physiologic sensors 156.Such sensors are commonly referred to as “rate-responsive” sensorsbecause they are typically used to adjust pacing stimulation ratesaccording to the exercise condition of the patient. However, thephysiological sensor 156 may further be used to detect changes incardiac output, changes in the physiological condition of the heart, ordiurnal changes in activity (e.g., detecting sleep and wake conditions).Signals generated by the physiological sensors 156 are passed to themicrocontroller 164 for analysis. The microcontroller 164 responds byadjusting the various pacing parameters (such as rate, AV Delay, V-VDelay, etc.) at which the atrial and ventricular pacing pulses areadministered. While shown as being included within the unit 100, thephysiologic sensor(s) 156 may be external to the unit 100, yet still beimplanted within or carried by the patient. Examples of physiologicsensors might include sensors that, for example, sense respiration rate,pH of blood, ventricular gradient, activity, position/posture, minuteventilation (MV), and so forth.

A battery 158 provides operating power to all of the components in theIMD 100. The battery 158 is capable of operating at low current drainsfor long periods of time, and is capable of providing high-currentpulses (for capacitor charging) when the patient requires a shock pulse(e.g., in excess of 2 A, at voltages above 2 V, for periods of 10seconds or more). The battery 158 also desirably has a predictabledischarge characteristic so that elective replacement time can bedetected. As one example, the IMD 100 employs lithium/silver vanadiumoxide batteries.

The IMD 100 further includes an impedance measuring circuit 160, whichcan be used for many things, including: lead impedance surveillanceduring the acute and chronic phases for proper lead positioning ordislodgement; detecting operable electrodes and automatically switchingto an operable pair if dislodgement occurs; measuring respiration orminute ventilation; measuring thoracic impedance for determining shockthresholds; detecting when the device has been implanted; measuringstroke volume; and detecting the opening of heart valves; and so forth.The impedance measuring circuit 160 is coupled to the switch 192 so thatany desired electrode may be used.

The IMD 100 can be operated as an implantable cardioverter/defibrillator(ICD) device, which detects the occurrence of an arrhythmia andautomatically applies an appropriate electrical shock therapy to theheart aimed at terminating the detected arrhythmia. To this end, themicrocontroller 164 further controls a shocking circuit 184 by way of acontrol signal 186. The shocking circuit 184 generates shocking pulsesof low (e.g., up to 0.5 joules), moderate (e.g., 0.5-10 joules), or highenergy (e.g., 111 to 50 joules), as controlled by the microcontroller164. Such shocking pulses are applied to the patient's heart throughshocking electrodes. It is noted that the shock therapy circuitry isoptional and may not be implemented in the IMD, as the various slavepacing units described below will typically not be configured to deliverhigh voltage shock pulses. On the other hand, it should be recognizedthat the slave pacing unit can be used within a system that includesbackup shock capabilities, and hence such shock therapy circuitry may beincluded in the IMD.

The microcontroller 164 is configured to execute the programinstructions to perform the operations described herein. Themicrocontroller 164 is configured to collect an EGM signal along one ormore sensing vector, where the EGM signal is associated with an event ofinterest. The microcontroller 164 is configured to determine an globalamplitude characteristic (GAC) and a global slope characteristic (GSC)from the EGM signal, to define a QRS start time, within the EGM signal,based on the GSC, and to determine a local amplitude characteristic(LAC) for a segment of the EGM signal within a search window of the GAC.The microcontroller 164 is configured to define a QRS end time, withinthe EGM signal, based on the LAC and calculate a QRS duration based onthe QRS start and QRS end. The GAC may represent a global amplitudeminimum experienced by the EGM signal over the event of interest, andthe GSC may represent a global slope minimum experienced by the EGMsignal over the event of interest. The microcontroller 164 may befurther configured to define the QRS start time as a last time pointalong the QRS complex before a point in time at which the GSC exhibitedat least one of: I) a slope of the EGM signal exceeds the global slopeminimum by a predetermined slope factor or II) the EGM signal exceedsthe global amplitude minimum by a predetermined amplitude factor. Themicrocontroller 164 may be further configured to calculate derivativesat points along the EGM signal over a search window that precedes theGAC and to determine the global slope minimum in a negative directionbased on the derivatives. The microcontroller 164 is configured toreduce the QRS start time by an amount corresponding to an isoelectricdrop. The determining of the LAC may comprise determining a localamplitude maximum that occurs within a time window after the GAC, andidentifying threshold crossings of the EGM signal that surround thelocal amplitude maximum, where the threshold crossings represent pointsat which the EGM signal cross a threshold amplitude that is definedbased on the local amplitude maximum.

Optionally, the microcontroller 164 determines the QRS end time tocorrespond to a point in time along the EGM signal at a set pointbetween the threshold crossings. Optionally, the microcontroller 164 isfurther configured to determine whether a deflection spike occurs priorto the QRS start time, and based thereon, verify whether the deflectionspike represents a local maximum amplitude. The microcontroller 164adjusts the QRS start time based on the verifying to a point in timebefore the deflection spike. Optionally, the microcontroller 164 isfurther configured to determine whether a deflection spike occurs priorto the QRS start time, and based thereon, verify whether a slope of theEGM signal within a time window prior to the deflection spike fallsbelow the global slope characteristic by a slope factor. Based on theverifying operation, the microcontroller 164 adjusts the QRS start timeto a point in time before the deflection spike. The operations of themicrocontroller 164 are described below in more detail.

QRS Duration Estimation

FIGS. 3A and 3B illustrate a process for estimating a duration of a QRScomplex from intracardiac electrograms in accordance with embodimentsherein. The operations of FIG. 3A are implemented by one or moreprocessors of the devices and systems described herein, such as an IMDand/or an external device.

At 302, the one or more processors collect intracardiac electrograms(EGM) signals in connection with one or more events of interest. By wayof example, the EGM signals may be collected by a leadless IMD, alead-based IMD coupled to one or more leads and/or an external devicecoupled to one or more implanted leads. The one or more leads haveelectrodes configured to be implanted proximate to regions of interest(e.g., within and/or surrounding the heart). Electrode combinations maybe selected to define sensing vectors of interest, where the sensingvectors (e.g., RV coil-to-can, RV coil-to-LV electrode) extend throughregions of interest. For example, the sensing vector may be between anRV coil electrode and a can/housing of an IMD. Additionally oralternatively, the sensing vector may be defined between electrodecombinations that are spaced with a desired portion, or a majority of,the heart between the electrodes. For example, the sensing vector may bebetween the RV coil and an LV electrode. Optionally, the sensing vectormay be between another RV electrode (e.g., tip or ring) and acan/housing of the IMD and/or an LV electrode. The electrodes may beconfigured to have a particular anode/cathode combination. For example,the RV coil electrode may be defined as the anode, while the can/housingof the IMD is defined as the cathode. The EGM signals are representativeof activity along the sensing vectors. The same or different electrodesmay be utilized to deliver CRT therapy in accordance with CRTparameters.

The collection operation at 302 may be performed in connection with asingle event of interest (e.g. one cardiac cycle or one beat).Additionally or alternatively, EGM signals may be collected for two ormore events of interest. When EGM signals are collected for more thanone event of interest, the EGM signals for each event/beat may beseparately analyzed as described hereafter in connection with FIGS. 3Aand 3B. Additionally or alternatively, the EGM signals for multipleevents/beats may be combined, such as to form an EGM ensemble (e.g.,average or other mathematical combination of multiple EGM signals).

At 304-310, the one or more processors analyze the EGM signal to definea QRS start time for a QRS complex. At 304, the one or more processorsanalyze an amplitude at multiple points along the EGM signal todetermine a global amplitude characteristic (GAC) from the EGM signal.For example, the GAC may represent a global amplitude minimumexperienced by the cardiac signal over the event of interest.

At 306 to 308, the one or more processors determine a global slopecharacteristic (GSC) from the EGM signal. For example, the GSC mayrepresent a global slope maximum experienced by the EGM signal over theevent of interest. At 306, the one or more processors calculatederivatives at points along the EGM signal over a desired search windowthat precedes the GAC. At 308, the one or more processors determine thenegative global slope minimum from the derivatives along the EGM signal.For example, the global slope minimum may represent a maximum negativedown stroke of the EGM signal.

At 310, the one or more processors define the QRS start time, within theEGM signal, based on the GSC. For example, as explained below inconnection with FIGS. 4A and 4B, when the GSC represents a global slopeminimum, the processors define the QRS start time as a last time pointalong the QRS complex before a point in time at which the GSC (e.g.,global slope minimum) exhibited at least one of the followingconditions: I) a derivative/slope of the EGM signal exceeds or isapproximately equal to a predetermined slope factor of the global slopeminimum and/or II) the EGM signal exceeds or is approximately equal to apredetermined amplitude factor of the global amplitude minimum. Forexample, one condition may be that a ratio of i) the dV/dt of the EGMsignal V(t) and ii) the global slope minimum dV/dt_(min) exceeds or isapproximately equal to 5%. The other condition may be that a ratio of i)the EGM signal V(t) and ii) the global amplitude minimum V_(min) exceedsor is approximately 10%. It is recognized that the foregoing slope andamplitude factors are examples and may vary.

Additionally or alternatively, the processors may define the QRS starttime at the point in time at which the GSC exhibits both of theforegoing conditions (I) and (II). Optionally, the QRS start time may beadjusted by a predefined amount to account for an isoelectric drop. Forexample, the QRS start time may be reduced by 5 ms (or some other amountthat is empirically defined) to account for the isoelectric drop.

At 312, the one or more processors determine whether to test for apotential deflection spike that may precede the QRS start time. When itis desirable to test for deflection spikes, flow branches to 314. Forexample, the determination at 312 may be based on a determination by theprocessors that the EGM signal exhibited a positive deflection orexceeded some baseline level before the global amplitude minimumdetermined at 304. As another option, the processors may base thedecision at 312 on a determination that the EGM signal exhibited a localamplitude maximum within a window surrounding the QRS start time and/orbefore the global amplitude minimum.

At 314, the one or more processors test for a deflection spike and whenpresent adjust the QRS start time. After 314, flow returns to 316.Optionally, the decision at 312 may be omitted and instead flow may movedirectly from 310 to 314. Optionally, the operations at 312 and 314 maybe omitted entirely.

At 316, the one or more processors determine a local amplitudecharacteristic (LAC) for the EGM signal within a select local searchwindow. The local amplitude characteristic may represent a localamplitude maximum exhibited by the EGM signal during the search window.The search window is positioned based on the GAC. For example, thesearch window may be set to a duration of 200 ms and may be alignedtemporally to begin at or shortly after the GAC (e.g., global amplitudeminimum). Optionally, a duration and start point of the search windowmay be varied.

At 318, the one or more processors identify two or more thresholdcrossings of the EGM signal. To do so, the processors define a thresholdamplitude based on the local amplitude maximum. For example, thethreshold amplitude may be defined to be a select percentage (e.g., 90%)of the LAC (e.g., local amplitude maximum). The processors identify atleast first and second points where the EGM signal crosses the thresholdamplitude, where the first and second points occur before and after theLAC. The first and second points are labeled as first and secondthreshold crossing points t₁ and t₂, and surround the local amplitudemaximum.

At 320, the one or more processors define a QRS end time, within the EGMsignal, based on the LAC. For example, the QRS endpoint is determined tocorrespond to a point in time along the EGM signal at a set distancebetween the first and second threshold crossing points t₁ and t₂. As afurther example, the QRS endpoint may be set at a desired distance alongthe range between the first and second threshold crossing points t₁ andt₂, such as 80% along the range between the first and second thresholdcrossing points t₁ and t₂.

At 322, the one or more processors calculate a QRS duration based on theQRS start point and QRS end point. For example, the QRS duration may beset to equal the time duration between the QRS start and end points.Additionally or alternatively, the QRS duration may be defined as apercentage (e.g., 90%, 110%) of the duration between the QRS start andend points. The QRS duration is saved in memory, such as in the IMD,external device, remote server and the like. The QRS duration may thenbe used for various reasons such as to determine whether a CRT therapyis effective or ineffective at achieving synchronous physiologicbehavior of the heart as explained below in connection with FIG. 3C.

Optionally, the operations of FIG. 3A may be performed periodically orupon demand from an external device, and/or based on indicators from thecardiac signals. For example, indications may be identified inconnection with monitoring whether a CRT therapy is effective orineffective. Optionally, the CRT therapy may be adjusted based on asingle QRS duration estimate and/or based on multiple iterations throughthe operations of FIGS. 3A and 3B over a period of time.

FIG. 3B illustrates a process for validating deflection spikes inaccordance with embodiments herein. As explained above, flow moves toFIG. 3B from 314 in FIG. 3A when it is desirable to determine whetherthe QRS start time is preceded by a deflection spike. Optionally, theoperations of FIG. 3B may be performed at other points within, before,or after the operations of FIG. 3A. (e.g., after 320 but before 322).

At 330, the one or more processors define a search window locatedproximate to the QRS start time (determined at 310 in FIG. 3A). Forexample, the search window (also referred to as a deflection spikesearch window) may be positioned to surround the QRS start time byextending back in time a desired duration and forward in time a desiredduration (e.g., starting 30 ms before the QRS start time and ending 10ms after the QRS start time). Optionally, the search window may bevaried in length and/or shifted to extend further back in time, or toextend a shorter distance back in time, preceding the QRS start time.The processors analyze the EGM signal segment within the search windowfor a characteristic of interest indicative of a deflection spike. Thecharacteristic of interest may represent a local amplitude maximumV_(max) ^(spike), in which case the processors analyze the EGM signal inthe search window to identify the local amplitude maximum.

At 332-342, the one or more processors analyze characteristics of theEGM signal segment that falls within the search window in order tovalidate or deny the deflection spike. The deflection spike isconsidered a “candidate” until validated or denied. By way of example, acharacteristic of interest may relate to whether the EGM signal ismonotonically increasing or decreasing over the search window. Asanother example, a characteristic of interest may relate to a slope ofthe EGM signal relative to the global slope minimum.

At 332, the one or more processors analyze the segment of the EGMsignal, within the deflection spike search window, surrounding the localamplitude maximum. The processors find a local amplitude maximum V_(max)^(spike) in the search window. The local amplitude maximum V_(max)^(spike) represents a maximum of an absolute value of the EGM signalV(t) in the search window. The processors determine whether the EGMsignal V(t) is monotonically increasing or decreasing from the localamplitude maximum V_(max) ^(spike) over all or a majority of the searchwindow. When the segment of the EGM signal monotonically increases ordecreases from the local amplitude maximum V_(max) ^(spike) over thesearch window, flow continues to 334. Otherwise, flow branches to 336.At 334, the one or more processors set a first deflection flag to afalse condition indicating that the EGM signal segment is notmonotonically changing. At 336, the one or more processors set thedeflection flag to a true condition indicating that the EGM signalsegment is monotonically changing. The analysis at 332 seeks todetermine whether the local amplitude maximum is indeed a local maximum,or instead merely a peak (e.g., at a leading or trailing end of thesearch window) along a continuously increasing or decreasing segment ofthe EGM signal. To have a local amplitude maximum, the EGM signal wouldnot monotonically increase or decrease across the search window.Accordingly, the one or more processors set a first deflection flag to atrue or false condition based on the determination at 332.

At 338, the one or more processors analyze a pre-spike search windowthat precedes the local amplitude maximum V_(max) ^(spike) to identify alocal slope maximum (dV/dt_(max) ^(spike)) of the segment of the EGMsignal within the pre-spike search window. For example, the pre-spikesearch window may be defined to extend 20 ms in length prior to thelocal amplitude maximum V_(max) ^(spike). The processors analyze a sloperatio between the local slope maximum dV/dt_(max) ^(spike) and theglobal slope minimum dV/dt_(min). The processors determine whether thelocal slope maximum dV/dt_(max) ^(spike) in the pre-spike search windowsatisfies a slope ratio condition relative to a global slopecharacteristic of the EGM signal. For example, the processors determinewhether the local slope maximum dV/dt_(max) ^(spike) is greater than apredetermined factor of the global slope minimum dV/dt_(min). Forexample, the processors may determine where the local slope maximumdV/dt_(max) ^(spike) within a 20 ms pre-spike search window is 30% ormore of the global slope minimum dV/dt_(min) (e.g., dV/dt_(max)^(spike)<(0.3)×(dV/dt_(min))). It is recognized that the durations ofthe windows and the size of the factors may be varied.

When the slope ratio condition at 338 is satisfied, flow branches to342. At 342, the one or more processors set a second deflection flag toa true condition. Alternatively, when the slope ratio condition at 338is not satisfied, flow continues to 340. At 340, the one or moreprocessors set the second deflection flag to a false condition.

Thereafter, flow moves to 344, where the one or more processorsdetermine whether one or both of the first and second deflection flagsare true. When both deflection flags are true, flow continues to 346.When one or both of the deflection flags are false, flow branches to348. At 348, flow returns to FIG. 3A. At 346, the one or more processorsadjust the QRS start time. For example, the processors may set the QRSstart time at a point in time, before the local amplitude maximumV_(max) ^(spike) identified at 330, where a slope in the EGM signalsatisfies a slope ratio relative to the local slope maximum dV/dt_(max)^(spike). For example, the QRS start time may be set to a point in timewhere the EGM signal has a slope that approximately equals or does notexceed 30% of the local slope maximum dV/dt_(max) ^(spike). Thereafter,flow moves to 348 and the process returns to FIG. 3A where the QRSduration is determined as explained in connection with FIG. 3A.

Next, the operations of FIGS. 3A-3B are described in connection withexample EGM signals of FIGS. 4A and 4B. FIG. 4A illustrates an exampleEGM signal for one cardiac cycle along with notations forcharacteristics of interest analyzed in accordance with embodimentsherein. In FIG. 4A, the EGM signal 400 extends over a cardiac cycle asnoted by bracket 402. The EGM signal 400 for the cardiac cycle isanalyzed to identify a global amplitude minimum V_(min) 404 (at 304 inFIG. 3A). Thereafter, the slope of the EGM signal 400 is identified atvarious points along the EGM signal over the cardiac cycle. The slopesat the various points are analyzed to identify a global slope minimum inthe negative direction dV/dt_(min) 406. Next, the process defines theQRS start time 408. For example, the QRS start time is defined as a lastpoint along the QRS complex before a point in time at which the globalslope minimum dV/dt_(min) exhibits at least one of two conditions. Forexample, one condition may be that a slope/derivative of the EGM signalV(t) exceeds or is approximately 5% of the negative global slope minimumdV/dt_(min). The other condition may be that the EGM signal V(t) exceedsor is approximately 10% of the global amplitude minimum V_(min). It isrecognized that the foregoing percentages are examples and may vary. Theconditions are found to be satisfied at the point denoted by 408.

FIG. 3C illustrates a process for determining synchrony or dyssynchronywithin physiologic behavior of the heart in accordance with embodimentsherein. At 370, the one or more processors obtain one or more QRSdurations. The QRS durations may be obtained from memory (such as whenstored during a prior iteration through FIG. 3A). Additionally oralternatively, at 370, the one or more processors may implement theprocess of FIG. 3A to collect new EGM signals and determine one or morecorresponding QRS durations.

At 372, the one or more processors compare the QRS duration to one ormore QRS duration thresholds to determine whether the QRS complex has a“broad” QRS complex or “narrow” QRS complex. A broad QRS complex is aQRS complex having a QRS duration that exceeds the correspondingthreshold is indicative of dyssynchrony within the physiologic behaviorof the heart. Dyssynchrony may indicate that a CRT therapy is noteffective. A narrow QRS complex, is a QRS complex having a QRS durationbelow the corresponding threshold is indicative of synchrony within thecardiac cycle. Synchrony may indicate that a CRT therapy is effective.

When the QRS duration exceeds the QRS duration threshold, flow branchesthree 376. When the QRS duration falls below the QRS duration threshold,flow continues to 374. At 374, the one or more processors of an IMD,external device and the like determine to maintain the CRT therapyconstant. At 376, the one or more processors adjust the CRT therapy byadjusting one or more CRT parameters.

In accordance with the operations of FIG. 3C, synchrony or dyssynchronyis declared based on whether the QRS duration falls below, equals orexceeds the QRS threshold. When a QRS duration exceeds the threshold andindicates dyssynchrony in the physiologic behavior of the heart, theIMD, external device or other processors within the system may determineto change one or more CRT parameters. For example, an IMD may adjust anatrioventricular delay, an interventricular delay, a pacing rate, and/orone or more other CRT parameters in an effort to determine a CRT therapythat achieves synchrony in the physiologic behavior of the heart.

In the example of FIG. 4A, the QRS start time is not preceded by anycandidate deflections spikes. More specifically, the portion of the EGMsignal that precedes the QRS start time 408 exhibits only negativeamplitudes and does not exceed the amplitude of the QRS start time 408.Accordingly, the optional operations of FIG. 4B are skipped.

Next, the process defines a search window 410 that follows the globalamplitude minimum 404. For example, a search window 410 may be definedto have a length of 200 ms following the global amplitude minimum 404.The EGM signal segment within the search window 410 is analyzed toidentify a local amplitude maximum 412. A threshold amplitude 414 isdefined based on the local amplitude maximum 412. For example, thethreshold amplitude 414 may be defined to equal 90% of the localamplitude maximum 412. The EGM signal segment surrounding the localamplitude maximum 412 is analyzed to identify first and second thresholdcrossings 416 and 418. Next, a QRS end time 420 is identified as a pointalong the EGM signal that is positioned a desired distance between thefirst and second threshold crossings 416 and 418. For example, the QRSendpoint 420 may be defined to correspond to a point along the EGMsignal that is approximately 80% across the distance between the firstand second threshold crossings 416 and 418. Based on the QRS start time408 and the QRS end time 420, a QRS duration is determined.

FIG. 4B illustrates an example EGM signal for one cardiac cycle alongwith notations for characteristics of interest analyzed in accordancewith embodiments herein. The EGM signal 450 is analyzed to identify aglobal amplitude minimum V_(min) 454. The slopes at the various pointsare analyzed to identify a global slope minimum in the negativedirection dV/dt_(min) 456. Next, the process defines an initial QRSstart time. However, the EGM signal includes a deflection peak 459 thatexist prior to the initial QRS start time, and thus the process of FIG.3B is implemented to test for a potential candidate deflection spike.

In connection with the process of FIG. 3B, a search window 461 isdefined proximate to an initial QRS start time. The EGM signal withinthe search window 461 is analyzed to identify a local amplitude maximum459 (V_(max) ^(spike)). The EGM signal within the search window 461 isfurther analyzed for the two conditions of interest. One condition iswhether the EGM signal is monotonically increasing or decreasing overthe search window 461. In the example of FIG. 4B, the EGM signal is notmonotonically increasing or decreasing, but instead includes a localmaximum at 459. As the second condition, the process analyzes apre-spike search window 463 that precedes the local amplitude maximum459. A local slope maximum 465 (dV/dt_(max) ^(spike)) is identified fromthe EGM segment within the pre-spike search window 463. Based thereon,the QRS start time 467 is identified as the point along the EGM signalwhere the slope satisfies a slope ratio. For example, the processdetermines a point along the EGM signal where the slope is 30% or moreof the global slope minimum 456 (dV/dt_(min)).

External Device

FIG. 5 illustrates a functional block diagram of the external device 500that is operated in accordance with the processes described herein andto interface with implantable medical devices as described herein. Theexternal device 500 may be a workstation, a portable computer, an IMDprogrammer, a PDA, a cell phone and the like. The external device 500includes an internal bus that connects/interfaces with a CentralProcessing Unit (CPU) 502, ROM 504, RAM 506, a hard drive 508, thespeaker 510, a printer 512, a CD-ROM drive 514, a floppy drive 516, aparallel I/O circuit 518, a serial I/O circuit 520, the display 522, atouch screen 524, a standard keyboard connection 526, custom keys 528,and a telemetry subsystem 530. The internal bus is an address/data busthat transfers information between the various components describedherein. The hard drive 508 may store operational programs as well asdata, such as waveform templates and detection thresholds.

The CPU 502 typically includes a microprocessor, a microcontroller, orequivalent control circuitry, designed specifically to controlinterfacing with the external device 500 and with the IMD 100. The CPU502 performs the QRS duration estimation process discussed above. TheCPU 502 may include RAM or ROM memory, logic and timing circuitry,condition machine circuitry, and I/O circuitry to interface with the IMD100. The display 522 (e.g., may be connected to the video display 532).The touch screen 524 may display graphic information relating to the IMD100. The display 522 displays various information related to theprocesses described herein. The touch screen 524 accepts a user's touchinput 534 when selections are made. The keyboard 526 (e.g., a typewriterkeyboard 536) allows the user to enter data to the displayed fields, aswell as interface with the telemetry subsystem 530. Furthermore, customkeys 528 turn on/off 538 (e.g., EVVI) the external device 500. Theprinter 512 prints copies of reports 540 for a physician to review or tobe placed in a patient file, and speaker 510 provides an audible warning(e.g., sounds and tones 542) to the user. The parallel I/O circuit 518interfaces with a parallel port 544. The serial I/O circuit 520interfaces with a serial port 546. The floppy drive 516 acceptsdiskettes 548. Optionally, the floppy drive 516 may include a USB portor other interface capable of communicating with a USB device such as amemory stick. The CD-ROM drive 514 accepts CD ROMs 550.

The telemetry subsystem 530 includes a central processing unit (CPU) 552in electrical communication with a telemetry circuit 554, whichcommunicates with both an EGM circuit 556 and an analog out circuit 558.The circuit 556 may be connected to leads 560. The circuit 556 is alsoconnected to the implantable leads 114, 116 and 118 to receive andprocess EGM cardiac signals as discussed above. Optionally, the EGMcardiac signals sensed by the leads 114, 116 and 118 may be collected bythe IMD 100 and then transmitted wirelessly to the telemetry subsystem530 input.

The telemetry circuit 554 is connected to a telemetry wand 562. Theanalog out circuit 558 includes communication circuits to communicatewith analog outputs 564. The external device 500 may wirelesslycommunicate with the IMD 100 and utilize protocols, such as Bluetooth,GSM, infrared wireless LANs, HIPERLAN, 3G, satellite, as well as circuitand packet data protocols, and the like. Alternatively, a hard-wiredconnection may be used to connect the external device 500 to the IMD100.

QRS Duration Estimation—Alternative Implementation

FIGS. 6A and 6B illustrate a process for estimating a duration of a QRScomplex from intracardiac electrograms in accordance with alternativeembodiments herein. The operations of FIGS. 6A and 6B are implemented byone or more processors of the devices and systems described herein, suchas an IMD and/or an external device. In accordance with embodimentsherein, it has been recognized that QRS start times and QRS end timesmaybe identified based on different criteria and/or from EGM signalscollected over different sensing vectors based upon whether intrinsicventricular activity is occurring and/or based on the pacing mode. Forexample, the QRS and time maybe identified based on different globalamplitude criteria depending upon whether the pacing mode is leftventricular multisite (LVMS) pacing, multipoint pacing (MPP),biventricular (BiV) pacing or left ventricular single site (LVSS)pacing.

At 602, the one or more processors collect EGM signals over first andsecond sensing vectors or channels in connection with one or more eventsof interest. By way of example, the EGM signals may be collected by aleadless IMD, a lead-based IMD coupled to one or more leads and/or anexternal device coupled to one or more implanted leads. The first andsecond sensing vectors/channels are configured to be sensitive todifferent aspects of cardiac behavior. For example, the first and secondsensing vectors/channels may correspond to near field and far fieldsensing vector/channels, respectively. Additionally or alternatively,the first and second sensing vector/channels may include one vectorextending through the RV and one or both atrium (e.g. a “RV coil-to-can”channel) and a second vector extending between the RV and the LV (e.g.an interventricular sensing vector).

The sensing vectors may be defined by first and second sets of circuitcomponents configured to have first and second sets of sensingparameters. For example, the first and second sensing channels may bedefined to have different frequency pass bands, sensitivity thresholdsand the like. The first and second sensing vectors or channels may becoupled to a common combination of electrodes and/or differentcombinations of electrodes that may include none, one or more commonelectrodes. As one example, the first channel may be defined by asensing vectors extending between an RV coil electrode and a canelectrode. As another example, the second channel may be defined bysensing vectors extending between an RV coil electrode and one or moreLV electrodes. Optionally, the sensing vector for the first channel maybe between another RV electrode (e.g., tip or ring) and a can/housing ofthe IMD and/or an LV electrode. The electrodes may be configured to havea particular anode/cathode combination. For example, the RV coilelectrode may be defined as the anode, while the can/housing of the IMDis defined as the cathode. The EGM signals are representative ofactivity along the sensing vectors. The same or different electrodes maybe utilized to deliver CRT therapy in accordance with CRT parameters.

The collecting operation at 602 may be performed in connection with asingle event of interest (e.g. one cardiac cycle or one beat).Additionally or alternatively, EGM signals may be collected for two ormore events of interest. When EGM signals are collected for more thanone event of interest, the EGM signals for each event/beat may beseparately analyzed as described hereafter in connection with FIGS. 6Aand 6B. Additionally or alternatively, the EGM signals for multipleevents/beats may be combined, such as to form an EGM ensemble (e.g.,average or other mathematical combination of multiple EGM signals).

At 604, the one or more processors define a QRS start time. For example,the QRS start time may be defined to correspond to the time associatedwith a marker corresponding to an intrinsic ventricular sensed event ora ventricular paced event. Additionally or alternatively, the QRS starttime may be defined based on the process described above in connectionwith FIGS. 3 and 4.

At 606, the one or more processors set a global characteristic (GC)search window, such as a global amplitude characteristic (GAC) searchwindow following the QRS start time. During the GC search window,various global characteristics of interest are identified from the EGMsignals collected over the first and second channels. By way of example,the GAC search window may be defined to have a predetermined length(e.g. 250 ms) and/or may be defined based on a relation to an RRinterval (e.g. a percentage of the RR interval).

At 608, the one or more processors define a first GC, namely a globalamplitude characteristic from the EGM signals collected over the firstchannel. For example, the channel-1 1^(st) GAC may represent an RV peakvalue. The RV peak value may be defined as the last point at which theEGM signal exhibits a positive slope before a crossing from a positiveslope to a negative slope. For example, the RV peak may be defined asthe last positive derivative/slope value in the EGM signals collectedalong the “RV coil-to-can” sensing vector that occurs within the GACsearch window following the QRS start time. Optionally, the first GC maynot be an absolute peak in the first EGM signal, but instead the RV peakvalue may correspond to a point at which the first EGM signal exceeds aprogrammed threshold, exceeds a level corresponding to a percentage of aprior RV peak and the like.

At 610, the one or more processors define a second GC, namely a secondglobal amplitude characteristic from the EGM signals collected over thefirst channel. For example, the channel-1 2^(nd) GAC may represent an RVvalley or minimum RV value. The RV valley or minimum value may bedefined as the point at which the channel-1 EGM signal where thederivative of the channel-1 EGM signal exhibits a last negative slope(e.g. dv/dt) prior to the point in time of the channel-1 first GAC. Forexample, the RV valley may be defined as the last negative slope (dv/dt)value in the EGM signals collected along the “RV coil-to-can” sensingvector prior to the RV peak. Optionally, the second GC may not be anabsolute minimum or valley in the first EGM signal, but instead the RVvalley value may correspond to a point at which the first EGM signaldrops below a programmed threshold, below a level corresponding to apercentage of a prior RV valley and the like.

At 612, the one or more processors define a third GC, namely a first GACfrom the EGM signals collected over the second channel. The channel-2first GAC may represent a low or minimal level of the EGM signal overthe second channel. For example, the channel-2 first GAC may representan LV valley corresponding to a global minimum in the EGM signalscollected along the “LV to RV coil” vector (e.g. interventricularvector). Optionally, the third GC may not be an absolute minimum orvalley in the second EGM signal, but instead the LV valley value maycorrespond to a point at which the second EGM signal drops below aprogrammed threshold, below a level corresponding to a percentage of aprior LV valley and the like.

Next, the discussion turns to FIG. 6B. FIG. 6B illustrates a method fordefining a QRS end time in accordance with embodiments herein. The endtime is defined based on different criteria depending upon theventricular pacing mode. At 630, the one or more processors determinethe ventricular pacing mode implemented while collecting the EGM signalsover the first and second channels. For example, the EGM signals may becollected during intrinsic ventricular activity, with no pacing, inwhich case flow moves to 636. Alternatively, the EGM signals may becollected while the device is providing left ventricular multisite(LVMS) pacing, or multipoint (MPP) pacing, in which case flow moves to634. For example, the MPP pacing may include delivering a pacing pulsefrom an RV electrode and a corresponding pacing pulses from multiple LVpacing sites. Alternatively, the LVMS pacing may include deliveringpacing pulses at multiple LV pacing sites (e.g. LV distal and LVproximal, LV distal and LVM1). Alternatively, the EGM signals may becollected while the device is providing biventricular (BiV) pacing orleft ventricular single site (LVSS) pacing, in which case flow moves to632. For example, during biventricular pacing, pacing pulses aredelivered in the RV and in the LV, with the pacing pulses timed in apredetermined manner (e.g. to achieve fusion pacing). As anotherexample, the LVSS pacing may represent pacing at a single LV site.

When the EGM signals are collected in connection with intrinsicventricular activity, at 636, the one or more processors define the QRSend time as the later point in time of either I) the channel-1 first GAC(RV peak) or II) the channel-2 first GAC (LV valley). For example, theQRS end time may be defined as the later end time of the point in timecorresponding to the RV peak or the point in time corresponding to theLV valley.

When the EGM signals are collected in connection with biventricular orLV single site pacing, at 632, the one or more processors determine athreshold crossing and compare at least one of the first, second andthird GC to the threshold crossing. For example, at 632, the one or moreprocessors designate the threshold crossing to correspond to a zerovoltage potential and compare the channel-1 first GAC to determinewhether the channel-1 first GAC is positive. For example, the decisionat 632 may determine whether an RV peak is positive, as measured fromEGM signals taken along an RV coil-to-can sensing vector. When thechannel-1 first GAC (RV peak) is positive, flow moves to 640. At 640,the one or more processors define the QRS end time as the time at whichthe channel-1 first GAC occurs (e.g. RV peak). Alternatively, when thechannel-1 first GAC is negative, flow moves to 638. At 638, the one ormore processors define the QRS end time as the time at which thechannel-1 second GAC (e.g. RV valley) occurs.

When the EGM signals are collected in connection with LV multisite ormultipoint pacing, at 634, the one or more processors determine athreshold crossing and compare at least one of the first, second andthird GC to the threshold crossing. For example, at 634, the one or moreprocessors designate the threshold crossing to correspond to twocriteria, namely i) a zero voltage potential and ii) a certainpercentage of the channel-1 second GAC. The one or more processorscompare the channel-1 first GAC to both threshold crossings to determinewhether the channel-1 first GAC i) is positive and ii) has an amplitudethat is equal to or greater than a predetermined percentage (e.g. 50%)of the channel-1 second GAC. For example, the one or more processors maydetermine whether the RV peak is positive as measured along a RVcoil-to-can sensing vector and whether the RV peak is at least 50% ofthe maximum of the RV valley. When the channel-1 first GAC has apositive value greater than or equal to the predetermined percentage,flow moves to 642. Otherwise, flow moves to 644. At 642, the one or moreprocessors define the QRS end time as the time at which the channel-1EGM signal reaches a set percentage (e.g. 50%) of the channel-1 firstGAC. For example, the QRS end time may be set at the time at which theEGM signal along the RV coil-to-can sensing vector reaches an amplitudeof approximately 50% of the RV peak. At 644, the one or more processorsdefine the QRS end time as the time at which the channel-1 EGM signalsreach a set percentage recovery following the channel-1 second GAC. Forexample, at 644, the QRS end time may be set as the time at which theEGM signal over an RV coil-to-can sensing vector recovers to aproximally 50% after an RV valley.

Thereafter, flow moves to 646. At 646, the one or more processors definethe QRS duration as the time difference between the QRS start time andQRS end time. The QRS duration is then saved for subsequent use.

Optionally, the operations of FIGS. 6A and 6B may be performedperiodically or upon demand from an external device, and/or based onindicators from the cardiac signals. For example, indications may beidentified in connection with monitoring whether a CRT therapy iseffective or ineffective. Optionally, the CRT therapy may be adjustedbased on a single QRS duration estimate and/or based on multipleiterations through the operations of FIGS. 6A and 6B over a period oftime.

Once the QRS duration is determined, flow moves to 372 (FIG. 3C) wherethe QRS duration is compared to a threshold. Based on the comparison,the process declares synchrony or dysynchrony and maintains or adjuststhe CRT parameters accordingly (as described in connection with FIG.3C). In accordance with embodiments, the QRS duration is then utilizedto program one or more CRT parameters, such as the atrioventricularand/or interventricular activation delays (AVD and VVD, respectively). Acardiovascular status of the patient may constantly change. Inaccordance with embodiments herein, methods and systems afford amechanism to maintain a desired (e.g. optimal) CRT parameters setthrough continuous evaluation of, and adaptation to, a currentcardiovascular status. Embodiments herein allow continuous amatorymonitoring of the cardiac response to CRT through closed-loopdevice-based alternatives to in clinic metrics. Device-based estimatesof surface ECG QRS durations are provided solely based on EGM's.

FIG. 7 illustrates examples of EGM signals collected over first andsecond sensing channels in connection with different intrinsic or pacingmodes. The upper panel in FIG. 7 illustrates intrinsic ventricularconduction, in which a first EGM signal is collected at 702 over asensing vector between an RV coil electrode and a can electrode, and asecond EGM signal is collected at 704 over a sensing vector between anLVM1 electrode and an RV coil electrode. In connection with theoperations of FIGS. 6A and 6B, a QRS start time is identified as thetime of the ventricular sense marker denoted Vs (708) corresponding to abeginning of an intrinsic ventricular event. Thereafter, a search window706 is defined following the QRS start time (e.g. 250 ms). The searchwindow 706 may be defined to begin immediately after the QRS start timeand/or set to begin some period of time after the QRS start time. Inconnection with the operations at 608-612, the processors analyze theEGM signals to define the channel-1 first GAC 710 (e.g. RV peak), secondGAC 712 (RV valley), and channel-2 first GAC 714 (LV valley). Next, theoperations of FIG. 6B follow the flow described above at 630 and 636 todefine the QRS end of time as the later of the channel-1 first GAC 710and channel to first GAC 714.

The middle panel in FIG. 7 illustrates a biventricular or LV single sitepacing mode, in which a EGM signal is collected at 722 over a sensingvector between an RV coil electrode and a can electrode, and a secondEGM signal is collected at 724 over a sensing vector between an LVD1electrode and an RV coil electrode. In connection with the operations ofFIGS. 6A and 6B, a QRS start time is identified as the time of theventricular pacing marker denoted Vp (728) corresponding to a beginningof a paced ventricular event. Thereafter, a peak search window (notshown) is defined following the QRS start time (e.g. 250 ms). Inconnection with the operations at 608-612, the processors analyze theEGM signals to define the channel-1 first GAC 730 (e.g. RV peak), andsecond GAC 732 (RV valley). Next, the operations of FIG. 6B follow theflow described above at 632, 638 and 640. At 632, the process determinesthat the channel-1 first GAC 730 is positive. Therefore, flow moves to640, where the QRS end time is set as the time of the channel-1 firstGAC 730.

The lower panel in FIG. 7 illustrates an LVMS or MPP pacing mode, inwhich a EGM signal is collected at 742 over a sensing vector between anRV coil electrode and a can electrode, and a second EGM signal iscollected at 744 over a sensing vector between an LVD1 electrode and anRV coil electrode. In connection with the operations of FIGS. 6A and 6B,a QRS start time is identified as the time of the ventricular pacingmarker denoted Vp (748) corresponding to a beginning of a pacedventricular event. Thereafter, a peak search window (not shown) isdefined following the QRS start time (e.g. 250 ms). In connection withthe operations at 608-612, the processors analyze the EGM signals todefine the channel-1 first GAC 750 (e.g. RV peak), and second GAC 752(RV valley). Next, the operations of FIG. 6B follow the flow describedabove at 634, 642 and 644. At 634, the process determines whether thechannel-1 first GAC 750 is positive and is greater than or equal to apredetermined percentage of the channel-1 second GAC 752. In the presentexample, the channel-1 first GAC 750 represents an RV peak that ispositive but does not exceed a predetermined percentage (e.g. 50%) ofthe RV valley associated with the channel-1 second GAC 752. Accordingly,in connection with FIG. 6B, flow moves from 634 to 644. At 644, the oneor more processors define the QRS end time as the time when thechannel-1 EGM signal reaches a predetermined recovery level 754 afterthe RV valley (channel-1 second GAC 752). 730 is positive.

It should be noted that in the foregoing description of FIG. 7, the EGMsignals collected over the second channels 724 and 744 are not analyzedfor a GAC value. Instead, the EGM signal collected over the secondchannel is only analyzed for a first GAC value in connection with anintrinsic ventricular conduction.

It is recognized that the EGM vectors and thresholds description hereinrepresent nonlimiting examples and were provided merely to demonstratepotential performance in a clinical setting, and that the methods andsystems described herein may be extended beyond the above examples. Forexample, while the foregoing discussion referred to a “RV Coil-to-Can”sensing vector, the “RV Ring-to-Can” sensing vector and/or otherfar-field EGM vectors could serve as alternative RV sensing vectors.Further, to calculate more representative QRSd values and reduce theimpact of natural beat-to-beat variation, EGM waveforms may be either(a) temporally filtered or (b) ensemble-averaged across multiple beatsbefore identifying QRS duration waveform features. Moreover, the QRSstart and end times may be utilized to calculate other QRScharacteristics in addition to or in place of QRS duration. For example,the QRS start and end times can be used as limits to calculate the QRS“area,” or integral (area under curve), which has been shown tocorrelate with electrical dyssynchrony. Also, while the presentdiscussion uses the “Vs” or “Vp” times as the start of the QRS duration,the morphology-based QRS start time may be utilized. Briefly, QRS startwas defined as the time of departure from baseline in the “RVCoil-to-Can” EGM.

Closing

It should be clearly understood that the various arrangements andprocesses broadly described and illustrated with respect to the Figures,and/or one or more individual components or elements of sucharrangements and/or one or more process operations associated of suchprocesses, can be employed independently from or together with one ormore other components, elements and/or process operations described andillustrated herein. Accordingly, while various arrangements andprocesses are broadly contemplated, described and illustrated herein, itshould be understood that they are provided merely in illustrative andnon-restrictive fashion, and furthermore can be regarded as but mereexamples of possible working environments in which one or morearrangements or processes may function or operate.

As will be appreciated by one skilled in the art, various aspects may beembodied as a system, method or computer (device) program product.Accordingly, aspects may take the form of an entirely hardwareembodiment or an embodiment including hardware and software that may allgenerally be referred to herein as a “circuit,” “module” or “system.”Furthermore, aspects may take the form of a computer (device) programproduct embodied in one or more computer (device) readable storagemedium(s) having computer (device) readable program code embodiedthereon.

Any combination of one or more non-signal computer (device) readablemedium(s) may be utilized. The non-signal medium may be a storagemedium. A storage medium may be, for example, an electronic, magnetic,optical, electromagnetic, infrared, or semiconductor system, apparatus,or device, or any suitable combination of the foregoing. More specificexamples of a storage medium would include the following: a portablecomputer diskette, a hard disk, a random access memory (RAM), a dynamicrandom access memory (DRAM), a read-only memory (ROM), an erasableprogrammable read-only memory (EPROM or Flash memory), a portablecompact disc read-only memory (CD-ROM), an optical storage device, amagnetic storage device, or any suitable combination of the foregoing.

Program code for carrying out operations may be written in anycombination of one or more programming languages. The program code mayexecute entirely on a single device, partly on a single device, as astand-alone software package, partly on single device and partly onanother device, or entirely on the other device. In some cases, thedevices may be connected through any type of network, including a localarea network (LAN) or a wide area network (WAN), or the connection maybe made through other devices (for example, through the Internet usingan Internet Service Provider) or through a hard wire connection, such asover a USB connection. For example, a server having a first processor, anetwork interface, and a storage device for storing code may store theprogram code for carrying out the operations and provide this codethrough its network interface via a network to a second device having asecond processor for execution of the code on the second device.

Aspects are described herein with reference to the figures, whichillustrate example methods, devices and program products according tovarious example embodiments. These program instructions may be providedto a processor of a general purpose computer, special purpose computer,or other programmable data processing device or information handlingdevice to produce a machine, such that the instructions, which executevia a processor of the device implement the functions/acts specified.The program instructions may also be stored in a device readable mediumthat can direct a device to function in a particular manner, such thatthe instructions stored in the device readable medium produce an articleof manufacture including instructions which implement the function/actspecified. The program instructions may also be loaded onto a device tocause a series of operational steps to be performed on the device toproduce a device implemented process such that the instructions whichexecute on the device provide processes for implementing thefunctions/acts specified.

The units/modules/applications herein may include any processor-based ormicroprocessor-based system including systems using microcontrollers,reduced instruction set computers (RISC), application specificintegrated circuits (ASICs), field-programmable gate arrays (FPGAs),logic circuits, and any other circuit or processor capable of executingthe functions described herein. Additionally or alternatively, themodules/controllers herein may represent circuit modules that may beimplemented as hardware with associated instructions (for example,software stored on a tangible and non-transitory computer readablestorage medium, such as a computer hard drive, ROM, RAM, or the like)that perform the operations described herein. The above examples areexemplary only, and are thus not intended to limit in any way thedefinition and/or meaning of the term “controller.” Theunits/modules/applications herein may execute a set of instructions thatare stored in one or more storage elements, in order to process data.The storage elements may also store data or other information as desiredor needed. The storage element may be in the form of an informationsource or a physical memory element within the modules/controllersherein. The set of instructions may include various commands thatinstruct the modules/applications herein to perform specific operationssuch as the methods and processes of the various embodiments of thesubject matter described herein. The set of instructions may be in theform of a software program. The software may be in various forms such assystem software or application software. Further, the software may be inthe form of a collection of separate programs or modules, a programmodule within a larger program or a portion of a program module. Thesoftware also may include modular programming in the form ofobject-oriented programming. The processing of input data by theprocessing machine may be in response to user commands, or in responseto results of previous processing, or in response to a request made byanother processing machine.

It is to be understood that the subject matter described herein is notlimited in its application to the details of construction and thearrangement of components set forth in the description herein orillustrated in the drawings hereof. The subject matter described hereinis capable of other embodiments and of being practiced or of beingcarried out in various ways. Also, it is to be understood that thephraseology and terminology used herein is for the purpose ofdescription and should not be regarded as limiting. The use of“including,” “comprising,” or “having” and variations thereof herein ismeant to encompass the items listed thereafter and equivalents thereofas well as additional items.

It is to be understood that the above description is intended to beillustrative, and not restrictive. For example, the above-describedembodiments (and/or aspects thereof) may be used in combination witheach other. In addition, many modifications may be made to adapt aparticular situation or material to the teachings herein withoutdeparting from its scope. While the dimensions, types of materials andcoatings described herein are intended to define various parameters,they are by no means limiting and are illustrative in nature. Many otherembodiments will be apparent to those of skill in the art upon reviewingthe above description. The scope of the embodiments should, therefore,be determined with reference to the appended claims, along with the fullscope of equivalents to which such claims are entitled. In the appendedclaims, the terms “including” and “in which” are used as theplain-English equivalents of the respective terms “comprising” and“wherein.” Moreover, in the following claims, the terms “first,”“second,” and “third,” etc. are used merely as labels, and are notintended to impose numerical requirements on their objects or order ofexecution on their acts.

What is claimed is:
 1. A method, comprising: under control of one ormore processors within an implantable medical device (IMD); collectingintra-cardiac electrogram (EGM) signals over first and second sensingchannels (channel-1 and channel-2 EGM signals, respectively) associatedwith an event of interest that includes a right ventricle (RV) and aleft ventricle (LV); determining first, second and third globalcharacteristics (GC) from the channel-1 and channel-2 EGM signals;defining a QRS start time within at least one of the EGM signals;determine a threshold crossing; comparing at least one of the first,second and third GC to the threshold crossing; selecting one of thefirst, second and third GC based on the comparing; defining a QRS endtime, within at least one of the channel-1 and channel-2 EGM signals,based on the comparing and based on the one of the first, second andthird GC selected; and calculating a QRS duration based on the QRS starttime and QRS end time.
 2. The method of claim 1, wherein the thresholdcrossing represents at least one of a positive-negative crossing or thethird GC, the third GC representing a global amplitude minimumexperienced by the channel-2 EGM signal over the event of interest. 3.The method of claim 1, wherein the first GC and second GC representfirst and second global amplitude characteristics (GAC) of the channel-1EGM signal, and the third GC represents a first GAC of the channel-2 EGMsignal.
 4. The method of claim 3, wherein first GAC represents an RVpeak, the second GAC represents an RV valley and the third GACrepresents an LV valley.
 5. The method of claim 1, further comprisingidentifying a pacing mode implemented when collecting the channel-1 andchannel-2 EGM signals, the comparing including comparing the at leastone of the first, second and third GC to different first and secondthreshold crossings based on the pacing mode.
 6. The method of claim 5,wherein, when the pacing mode is one of a left ventricular multi-sitepacing or multi-point pacing, the threshold crossing corresponding tothe first GC having a value that is both positive and greater than orequal to a select percentage of the second GC.
 7. The method of claim 5,wherein, when the pacing mode is one of biventricular pacing or leftventricular single site pacing, the threshold crossing corresponding tothe first GC having a value that is positive.
 8. The method of claim 5,wherein, when the pacing mode is one of a left ventricular multi-sitepacing or multi-point pacing, the defining including defining the QRSend as either i) a time when the channel-1 EGM signal reaches a setrelation to an RV peak corresponding to the first GC or ii) a time whenthe channel-1 EGM signal reaches a set recovery relation to an RV valleycorresponding to the second GC.
 9. The method of claim 5, wherein, whenthe pacing mode is one of biventricular pacing or left ventricularsingle site pacing, the defining including defining the QRS end aseither i) a time when the channel-1 EGM signal reaches an RV peakcorresponding to the first GC or ii) a time when the channel-1 EGMsignal reaches an RV valley corresponding to the second GC.
 10. Themethod of claim 1, wherein the first and third GC corresponding to an RVpeak in the channel-1 EGM signal and an LV valley in the channel-2 EGMsignal, respectively, the method further comprising identifying that thechannel-1 and channel-2 EGM signals were collected during intrinsicventricular activity, and based thereon defining the QRS end as a latertime of the RV peak and the LV valley.
 11. A system comprising:electrodes configured to be located proximate to a heart, the electrodesdefining channel-1 and channel-2 sensing channels through a region ofinterest in the heart that includes a right ventricle (RV) and a leftventricle (LV); memory to store program instructions; and a processorthat, when executing the program instructions, is configured to: collectintra-cardiac electrogram (EGM) signals over first and second sensingchannels (channel-1 and channel-2 EGM signals, respectively) associatedwith an event of interest; determine first, second and third globalcharacteristics (GC) from the channel-1 and channel-2 EGM signals;define a QRS start time within at least one of the EGM signals;determine a threshold crossing; compare at least one of the first,second and third GC to the threshold crossing; select one of the first,second and third GC based on the comparing; define a QRS end time,within at least one of the channel-1 and channel-2 EGM signals, based onthe comparing and based on the one of the first, second and third GCselected; and calculate a QRS duration based on the QRS start time andQRS end time.
 12. The system of claim 11, wherein the processor isconfigured to identify the threshold crossing as at least one of apositive-negative crossing or the third GC, the third GC representing aglobal amplitude minimum experienced by the channel-2 EGM signal overthe event of interest.
 13. The system of claim 11, wherein the processoris configured to define the first GC and second GC as first and secondglobal amplitude characteristics (GAC) of the channel-1 EGM signal, anddefine the third GC as a first GAC of the channel-2 EGM signal.
 14. Thesystem of claim 13, wherein first GAC represents an RV peak, the secondGAC represents an RV valley and the third GAC represents an LV valley.15. The system of claim 11, wherein the processor is configured toidentify a pacing mode implemented when collecting the channel-1 andchannel-2 EGM signals, the compare the at least one of the first, secondand third GC to different first and second threshold crossings based onthe pacing mode.
 16. The system of claim 15, wherein, when the pacingmode is one of a left ventricular multi-site pacing or multi-pointpacing, the processor is configured to designate the threshold crossingto correspond to the first GC having a value that is both positive andgreater than or equal to a select percentage of the second GC.
 17. Thesystem of claim 15, wherein, when the pacing mode is one ofbiventricular pacing or left ventricular single site pacing, theprocessor is configured to designate the threshold crossing tocorrespond to the first GC having a value that is positive.
 18. Thesystem of claim 15, wherein, when the pacing mode is one of a leftventricular multi-site pacing or multi-point pacing, the processor isconfigured to define the QRS end as either i) a time when the channel-1EGM signal reaches a set relation to an RV peak corresponding to thefirst GC or ii) a time when the channel-1 EGM signal reaches a setrecovery relation to an RV valley corresponding to the second GC. 19.The system of claim 15, wherein, when the pacing mode is one ofbiventricular pacing or left ventricular single site pacing, theprocessor is configured to define the QRS end as either i) a time whenthe channel-1 EGM signal reaches an RV peak corresponding to the firstGC or ii) a time when the channel-1 EGM signal reaches an RV valleycorresponding to the second GC.
 20. The system of claim 11, wherein theprocessor is configured to designate the first and third GC tocorrespond to an RV peak in the channel-1 EGM signal and an LV valley inthe channel-2 EGM signal, respectively, the processor is configured toidentify that the channel-1 and channel-2 EGM signals were collectedduring intrinsic ventricular activity, and based thereon define the QRSend as a later time of the RV peak and the LV valley.